scholarly journals Biocompatibility and patency of a novel titanium vascular anastomotic device in a pig jugular vein

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sanghyun An ◽  
Junsik Kim ◽  
Donghyun Lee ◽  
Minwoo Kim ◽  
Kangil Byun ◽  
...  
Keyword(s):  
Jugular Vein ◽  
Ex Vivo ◽  
Graft Patency ◽  
Anastomotic Site ◽  
Jugular Veins ◽  
Promising Tool ◽  
Vessel Lumen ◽  
Pure Grade ◽  
Inner Vessel

AbstractThis study aimed to evaluate the biocompatibility and patency of our newly developed titanium vascular anastomotic device (TVAD) in a pig jugular vein. TVAD was made of commercially pure grade 2 titanium. The patency and anastomotic time were simultaneously confirmed in an ex-vivo system developed by the authors and in vivo using pig jugular veins. Five 8-month-old pigs, with body weights of 50–60 kg, underwent anastomosis of both jugular veins using the device. Graft patency was evaluated for 12 weeks by biplane angiography and sonography. All tissue biopsy samples were analysed by histology. In all 10 cases, the anastomosis was completed in < 5 min. The vessel lumen was not damaged, and the inner vessel wall was completely endothelialised at the anastomotic site. No foreign body reactions were observed at the vessel lumen, vessels, and outer vessel walls by histopathologic analysis. Patency and absence of leakage at the anastomotic site of the follow-up period were confirmed clearly by angiography and sonography. This preliminary animal study proved that our newly developed device is a very promising tool for intima-to-intima contact anastomosis. TVAD can be used as a feasible and safe medical tool for vessel anastomosis.

RPR120844, a Novel, Specific Inhibitor of Coagulation Factor Xa Inhibits Venous Thrombosis in the Rabbit

1999 ◽  
Vol 81 (01) ◽  
pp. 157-160 ◽  
Author(s):  
Ross Bentley ◽  
Suzanne Morgan ◽  
Karen Brown ◽  
Valeria Chu ◽  
Richard Ewing ◽  
...  
Keyword(s):  
Jugular Vein ◽  
Drug Effect ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Specific Inhibitor ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Antithrombotic Activity ◽  
Fxa Inhibitor

SummaryThe in vivo antithrombotic activity of RPR120844, a novel synthetic coagulation factor Xa (fXa) inhibitor (Ki = 7 nM), was assessed by its ability to inhibit thrombus formation in a damaged segment of the rabbit jugular vein. Intravenous dose-response studies were performed and thrombus mass (TM), activated partial thromboplastin time (APTT), prothrombin time (PT), inhibition of ex vivo fXa activity and plasma drug levels (PDL) were determined. TM, measured at the end of a 50 min infusion, was significantly reduced (p <0.05 vs saline-treated animals) by RPR120844 at 30 and 100 μg/kg/min. At doses of 10, 30 and 100 μg/kg/min, APTT was prolonged by 2.1, 4.2 and 6.1-fold, and PT was prolonged by 1.4, 2.2 and 3.5-fold, respectively. PDL were determined by measuring anti-fXa activity using an amidolytic assay. Peak PDL were 0.8 ± 0.3, 1.5 ± 0.9 and 2.4 ± 0.6 μM, respectively. The drug effect was reversible with APTT, PT and PDL returning toward pretreatment values 30 min after termination of treatment. The results suggest that RPR120844, or similar compounds, may provide an efficacious, yet easily reversible, means of inhibiting thrombus formation.

scholarly journals Raman spectroscopy as a promising noninvasive tool in brain cancer detection

2017 ◽  
Vol 10 (05) ◽  
pp. 1730012 ◽  
Author(s):  
Piyush Kumar
Keyword(s):  
Raman Spectroscopy ◽  
Cancer Detection ◽  
Ex Vivo ◽  
Human Subjects ◽  
Intensive Therapy ◽  
Brain Tumor Surgery ◽  
Noninvasive Technique ◽  
Therapy Regimen ◽  
Promising Tool

Despite intensive therapy regimen, brain cancers present with a poor prognosis, with an estimated median survival time of less than 15 months in case of glioblastoma. Early detection and improved surgical resections are suggested to enhance prognosis; several tools are being explored to achieve the purpose. Raman spectroscopy (RS), a nondestructive and noninvasive technique, has been extensively explored in brain cancers. This review summarizes RS-based studies in brain cancers, categorized into studies on animal models, ex vivo human samples, and in vivo human subjects. Findings suggest RS as a promising tool which can aid in improving the accuracy of brain tumor surgery. Further advancements in instrumentation, market-assessment, and clinical trials can facilitate translation of the technology as a noninvasive intraoperative guidance tool.

A COMPARISON BETWEEN FIBRINOLYSIS OF FRESH AND AGED CLOTS OR THROMBI BY rt-PA IN VIVO, EX VIVO AND IN VITRO

1987 ◽  
Author(s):  
U Nauland ◽  
W Haarmann ◽  
T H Müller ◽  
W G Eisert
Keyword(s):  
Carotid Artery ◽  
Whole Blood ◽  
Jugular Vein ◽  
Ex Vivo ◽  
Clot Retraction ◽  
Therapeutic Applications ◽  
Blood Clots ◽  
Better Than

In view of the therapeutic applications of rt-PA it is of interest to investigate whether there is any difference in the lysability between fresh and aged thrombi. The efficiency of fibrinolysis by rt-PA was studied in 3 different ways: In vivo, by measuring the thrombus weight of fresh (1 h) or aged (24 h) thrombi in the carotid artery of rabbits which had been treated with rt-PA (0.4 mg/kg) or saline for 1 h. Ex vivo, by measuring I125-release of in vivo fresh (1 h) and aged (24 h) thrombi (labelled with I125-fibrinogen) suspended in vitro in plasma containing rt-PA (1 μg/ml) ; the thrombi were formed in the jugular vein and the carotid artery of each rabbit. In vitro, by measuring I125-release of fresh (1 h) and aged (6 or 24 h) human native whole blood clots, PPP-clots, PRP-clots and squeezed PPP-clots which were formed and lysed in vitro with rt-PA (1 μg/ml) . In vivo as well as ex vivo rt-PA lysed fresh (1 h) thrombi much better than aged (24 h) thrombi. This difference was more pronounced immediately after the onset of fibrinolysis, but decreased with time. However, in vitro relatively little difference was observed in fibrinolysis efficiency between fresh (1 h) and aged (6 or 24 h) clots; fibrinolysis of these clots was decreased (PPP > whole blood > PRP) with increasing clot retraction, which was almost complete within 1 h. This result was also confirmed when PPP-clots were “retracted” by simply squeezing them just before lysis. Therefore we conclude that a considerable difference in lysis efficiency between fresh and aged thrombi was only observed when thrombi were formed and aged in vivo. This difference was less pronounced with increasing fibrinolysis time.

Cyclosporin A-loaded poly(d,l-lactide) nanoparticles: a promising tool for treating alopecia

Nanomedicine ◽  
2020 ◽  
Vol 15 (15) ◽  
pp. 1459-1469
Author(s):  
Bruno Fernandes ◽  
Teresa Matamá ◽  
Andreia C. Gomes ◽  
Artur Cavaco-Paulo
Keyword(s):  
Cyclosporin A ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Hair Follicles ◽  
Porcine Skin ◽  
Skin Cell ◽  
Promising Tool ◽  
Physicochemical Stability ◽  
New Strategy

Background: Alopecia treatments are scarce and lack efficacy. Cyclosporin A (CsA) has hair growth-inducing properties but its poor cutaneous absorption undermines its use in topical treatments. Aim: Development of a new potential topical treatment of alopecia with CsA. Materials & methods: CsA-loaded poly(d,l-lactide) (PLA) nanoparticles were obtained and characterized. Skin permeation was evaluated in ex vivo porcine skin. Results: Nanoparticles with good physicochemical stability increased CsA skin permeation/hair follicles accumulation, compared with a noncolloidal formulation. CsA biocompatibility in NCTC2455 keratinocytes (reference skin cell line) was clearly improved when encapsulated in PLA nanoparticles. Conclusion: This work fosters further in vivo investigation of CsA-loaded PLA nanoparticles as a promising new strategy to treat alopecia, a very traumatic, possibly autoimmune, disease.

scholarly journals Interrelationships between structure and function during the hemostatic response to injury

2019 ◽  
Vol 116 (6) ◽  
pp. 2243-2252 ◽  
Author(s):  
Maurizio Tomaiuolo ◽  
Chelsea N. Matzko ◽  
Izmarie Poventud-Fuentes ◽  
John W. Weisel ◽  
Lawrence F. Brass ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Ex Vivo ◽  
Antiplatelet Agents ◽  
Coagulation Factors ◽  
Jugular Veins ◽  
Spatial Regulation ◽  
Injury Model ◽  
And Function ◽  
Damaged Vessel

Extensive studies have detailed the molecular regulation of individual components of the hemostatic system, including platelets, coagulation factors, and regulatory proteins. Questions remain, however, about how these elements are integrated at the systems level within a rapidly changing physical environment. To answer some of these questions, we developed a puncture injury model in mouse jugular veins that combines high-resolution, multimodal imaging with functional readouts in vivo. The results reveal striking spatial regulation of platelet activation and fibrin formation that could not be inferred from studies performed ex vivo. As in the microcirculation, where previous studies have been performed, gradients of platelet activation are readily apparent, as is an asymmetrical distribution of fibrin deposition and thrombin activity. Both are oriented from the outer to the inner surface of the damaged vessel wall, with a greater extent of platelet activation and fibrin accumulation on the outside than the inside. Further, we show that the importance of P2Y12signaling in establishing a competent hemostatic plug is related to the size of the injury, thus limiting its contribution to hemostasis to specific physiologic contexts. Taken together, these studies offer insights into the organization of hemostatic plugs, provide a detailed understanding of the adverse bleeding associated with a widely prescribed class of antiplatelet agents, and highlight differences between hemostasis and thrombosis that may suggest alternative therapeutic approaches.

scholarly journals Cardiac Optical Mapping in Situ in Swine Models: A View of the Current Situation

Medicina ◽  
2020 ◽  
Vol 56 (11) ◽  
pp. 620
Author(s):  
Irma Martišienė ◽  
Regina Mačianskienė ◽  
Rimantas Benetis ◽  
Jonas Jurevičius
Keyword(s):  
Electrical Activity ◽  
Optical Mapping ◽  
Ex Vivo ◽  
Isolated Heart ◽  
Spatiotemporal Resolution ◽  
Electrophysiological Properties ◽  
Promising Tool ◽  
Large Animals

Optical mapping is recognized as a promising tool for the registration of electrical activity in the heart. Most cardiac optical mapping experiments are performed in ex vivo isolated heart models. However, the electrophysiological properties of the heart are highly influenced by the autonomic nervous system as well as humoral regulation; therefore, in vivo investigations of heart activity in large animals are definitely preferred. Furthermore, such investigations can be considered the last step before clinical application. Recently, two comprehensive studies have examined optical mapping approaches for pig hearts in situ (in vivo), likely advancing the methodological capacity to perform complex electrophysiological investigations of the heart. Both studies had the same aim, i.e., to develop high-spatiotemporal-resolution optical mapping suitable for registration of electrical activity of pig heart in situ, but the methods chosen were different. In this brief review, we analyse and compare the results of recent studies and discuss their translational potential for in situ cardiac optical mapping applications in large animals. We focus on the modes of blood circulation that are employed, the use of different voltage-sensitive dyes and their loading procedures, and ways of eliminating contraction artefacts. Finally, we evaluate the possible scenarios for optical mapping (OM) application in large animals in situ and infer which scenario is optimal.

Augmentation of the Anticoagulant Effects of Heparin By a Tri-Block Polymer MST-188

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5080-5080
Author(s):  
Daniel Dansdill ◽  
Jae Cho ◽  
Daneyal Syed ◽  
Jawed Fareed ◽  
Martin Emanuele
Keyword(s):  
Blood Vessel ◽  
Bleeding Time ◽  
Jugular Vein ◽  
Ex Vivo ◽  
Rat Plasma ◽  
Acute Limb Ischemia ◽  
Thrombin Time ◽  
Blood Samples

Abstract Introduction: MST-188 (purified poloxamer 188) is a tri-block co-polymer with high affinity to hydrophobic cellular surfaces that inhibits hydrophobic adhesive interactions in the circulation. It also facilitates blood flow by reducing blood viscosity and reportedly exhibits anti-adhesion and anti-inflammatory properties. Currently, this agent is under study in with patients experiencingsickle cell crisis and in patients with acute limb ischemia. Since MST-188 may be administered with other anti-coagulant agents such as heparin its potential interaction to modulate the anti-coagulant effects of this drug require experimental validation. These studies are designed to investigate the potential interactions between heparin and MST-188 in a rat model of tail transection bleeding and jugular vein clamping induced thrombosis model. Materials and Methods: The in vitro interactions between MST-188 were investigated by supplementing this agent to normal rat plasma (NRP) and heparinized rat plasma at a fixed concentrations of 1.25 and 2.50 mg/mL. The concentration of heparin was kept at 1.25 and 2.50 μg/mL. In the in vivo studies individual groups of rats (n=6-8) were administered with saline as a control, heparin in the dosage range of 125-500 ug/kg intravenously and MST-188 at 25 mg/kg IV followed by heparin at the 125-500 ug/kg dosages. Rat tail resection time was measured 5 minutes after administration of heparin and clot occlusion index was measured as number of jugular vein clamping required to occlude the blood vessel. After the completion of the procedure blood samples were obtained through cardiac puncture and used for ex vivo analysis of PT, aPTT, heptest and thrombin time. Results: In the in vitro studies heparin produced a concentration dependent prolongation of the aPTT, heptest and thrombin time. MST-188 did not produce any effects on the aPTT and heptest time, however it decreased the thrombin time. MST-188 at a higher concentration of 2.5 and 5.0 mg/ml produced a shorting of heparins anticoagulant responses, as measured by aPTT and thrombin time. Heparin produced a dose dependent increase in both the bleeding time (p<0.0001) and number of jugular vein clamps to occlude the blood vessel (p<0.0001). MST-188 at dosages of 25 mg/kg produced a significant increase on both bleeding time (p <0.05) and number of clampings required to occlude the blood vessel (p<0.0001). When MST-188 was administered simultaneously with heparin it augmented the bleeding time (p < 0.05) and increased the number of jugular vein clamps required to occlude the blood vessel (p < 0.05). The ex vivo analysis of blood samples collected from rats treated in different regimens did not exhibit any anti-coagulant effects as measured by PT, aPTT, heptest and thrombin time. Conclusion: These studies suggest a differential response of MST-188. While in vitro it exhibits a prohemostatic response as evident by shortening of thrombin time, in the in vivo setting it enhances the anticoagulant effects of heparin as evident by increased bleeding time and increased number of jugular vein clamps required to occlude the vessel. Thus, both of these mechanisms are involved in the mediation of the beneficial effects observed with this agent in vaso-occlusive and thrombotic processes. Disclosures Emanuele: Mast Therapeutics: Employment.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Antithrombotic Effects and Bleeding Time Prolongation with Synthetic Platelet GPIIb/llla Inhibitors in Animal Models of Platelet-Mediated Thrombosis

1994 ◽  
Vol 71 (01) ◽  
pp. 095-102 ◽  
Author(s):  
Désiré Collen ◽  
Hua Rong Lu ◽  
Jean-Marie Stassen ◽  
Ingrid Vreys ◽  
Tsunehiro Yasuda ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Bleeding Time ◽  
Bolus Injection ◽  
Cell Injury ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Femoral Vein ◽  
Thrombotic Occlusion ◽  
Antithrombotic Effects

SummaryCyclic Arg-Gly-Asp (RGD) containing synthetic peptides such as L-cysteine, N-(mercaptoacetyl)-D-tyrosyl-L-arginylglycyl-L-a-aspartyl-cyclic (1→5)-sulfide, 5-oxide (G4120) and acetyl-L-cysteinyl-L-asparaginyl-L-prolyl-L-arginyl-glycyl-L-α-aspartyl-[0-methyltyrosyl]-L-arginyl-L-cysteinamide, cyclic 1→9-sulfide (TP9201) bind with high affinity to the platelet GPIIb/IIIa receptor.The relationship between antithrombotic effect, ex vivo platelet aggregation and bleeding time prolongation with both agents was studied in hamsters with a standardized femoral vein endothelial cell injury predisposing to platelet-rich mural thrombosis, and in dogs with a carotid arterial eversion graft inserted in the femoral artery. Intravenous administration of G4120 in hamsters inhibited in vivo thrombus formation with a 50% inhibitory bolus dose (ID50) of approximately 20 μg/kg, ex vivo ADP-induccd platelet aggregation with ID50 of 10 μg/kg, and bolus injection of 1 mg/kg prolonged the bleeding time from 38 ± 9 to 1,100 ± 330 s. Administration of TP9201 in hamsters inhibited in vivo thrombus formation with ID50 of 30 μg/kg, ex vivo platelet aggregation with an ID50 of 50 μg/kg and bolus injection of 1 mg/kg did not prolong the template bleeding time. In the dog eversion graft model, infusion of 100 μg/kg of G4120 over 60 min did not fully inhibit platelet-mediated thrombotic occlusion but was associated with inhibition of ADP-induccd ex vivo platelet aggregation and with prolongation of the template bleeding time from 1.3 ± 0.4 to 12 ± 2 min. Infusion of 300 μg/kg of TP9201 over 60 min completely prevented thrombotic occlusion, inhibited ex vivo platelet aggregation, but was not associated with prolongation of the template bleeding time.TP9201, unlike G4120, inhibits in vivo platelet-mediated thrombus formation without associated prolongation of the template bleeding time.

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